In recent years, on annual basis, more than 10 million people have been diagnosed as having a malignant tumor, and more than 7 million people die of malignant tumor, and the numbers tend to increase. Correct diagnosis, appropriate treatment, evaluation of the effect of the treatment, and prediction and prevention of recurrence of malignant tumor are thought to be important factors for malignant tumor patients to survive. Currently, in order to obtain valuable information therefor, histopathological diagnosis, genetic testing, diagnostic imaging, blood-basis clinical tests, etc. are carried out singly or in combination. In particular, the determination of tumor marker level in a blood sample is a convenient and relatively inexpensive testing method.
Malignant tumors are generally classified into carcinoma and sarcoma. According to the new WHO classification, a hematopoietic tumor, which is a type of sarcoma, is generally divided into leukemia and malignant lymphoma. Leukemia is divided into acute leukemia (rapid growing) and chronic leukemia (slow growing), and acute leukemia is divided into acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML). ALL is further divided, on the basis of cell type, into T-cell ALL and B-cell ALL.
In the case where the blast level in bone marrow is 20% or higher, the condition is diagnosed as AML, and in the case where the blast level in bone marrow is lower than 20%, the condition is diagnosed as myelodysplastic syndrome (MDS).
In the case of acute leukemia (AL), immediate start of the treatment therefor is essential, since it shows rapid progression. When AL or recurrence thereof is suspected, bone marrow cells are analyzed through bone marrow aspiration for definite diagnosis. However, this test cannot be used frequently since it is very invasive to the patients.
In chronic leukemia (CL), which differs from AL in that differentiation and maturation ability is maintained, chronic myeloid leukemia (CML) is classified as a myeloproliferative disorder (MPD), and chronic lymphocytic leukemia (CLL) is classified as a malignant lymphoma. CL does not have specific symptoms and progresses slowly. However, since CL may sometimes become AL (acute conversion) in the long term, periodic observation is required during and after the treatment.
Meanwhile, malignant lymphoma is generally classified into Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL).
In Japan, about 90% of malignant lymphoma cases are NHL, and there are often observed follicular lymphoma, which is a low-grade and slow growing lymphoma, and diffuse large B-cell lymphoma, which is a medium-grade and rapid growing lymphoma. The treatment of NHL varies depending on the classified stage and malignancy grade. Among lymphoma cases, particularly, low-grade lymphoma progresses slowly and is less susceptible to treatment, and increase in malignancy and transition to leukemia may occur. Therefore, careful follow-up observation of symptoms of low-grade lymphoma is required.
Malignant lymphoma occurs at lymph nodes as foci. Since lymph nodes are present throughout the body, the focal sites of malignant lymphoma are difficult to find, as compared with the case of leukemia. Particularly in the case of recurrence thereof, specific focal sites are difficult to detect in reality. Therefore, it is very important to determine the focal site and scale of the pathological condition in the body, requiring expensive diagnostic imaging such as CT, MRI, or PET and highly invasive bone marrow aspiration.
In order to assess the expansion and strength of the disease and the effect of the treatment therefor, blood test for lactate dehydrogenase (LDH), C-reactive protein (CRP), β2-microglobulin, ferritin, soluble interleukin-2 receptor (sIL-2R), etc. is carried out. However, test values for these blood analysis items are known to rise by liver malfunction, kidney mal-function, bacterial infection, and collagen diseases such as rheumatoid arthritis and SLE. Therefore, these test value-raising factors must be carefully taken into consideration when hematopoietic tumor is diagnosed based on the above-described blood analysis items.
In clinical examination, tumor markers such as α-fetoprotein, CEA, and CA19-9 are employed to detect carcinomas such as liver cancer, pancreatic cancer, colon cancer, etc. When any of these markers is employed singly, in many cases, organ-specificity and malignant tumor detection sensitivity are insufficient. Thus, a plurality of tumor markers are often assayed in combination, and therefore, there is demand for development of an assay item which can serve as a new tumor marker.
LR11 (LDL receptor relative with 11 ligand-binding repeats) was a novel LDL receptor-like protein identified as having a characteristic structure to the LDL receptor family (Patent Document 1 and Non-Patent Document 1). Expression of LR11 is reported to be promoted particularly in vascular intima thickened sites generated by migration and proliferation of smooth muscle cells (Non-Patent Document 2). Furthermore, the following are also known: soluble LR11 is present in blood of mammals; the level of soluble LR11 of arteriosclerosis disease patients is significantly higher than that of healthy subjects (Patent Document 2); and soluble LR11 level is an independent factor which defines the intima media thickness (IMT) (Non-Patent Document 3). Moreover, there is also known a method for readily and correctly determining the soluble LR11 level in blood and cerebrospinal fluid (Patent Document 3, Non-Patent Document 4).